Rosiglitazone inhibits migration, proliferation, and phenotypic differentiation in cultured human lung fibroblasts

Recent studies have indicated that peroxisome proliferator-activated receptor gamma (PPAR gamma) is capable of modulating inflammation, which prompted us to investigate the potential of PPAR gamma ligands as lung protective agents in pulmonary fibrosis. The present study was undertaken to investigate the effects of rosiglitazone (RSG), a highly potent ligand of PPAR gamma, on migration, proliferation, and phenotypic differentiation of human lung fibroblasts (MRC-5) and to explore its potential for therapy of pulmonary fibrosis. The cell migration potential was observed in a scratch wound model. Cell proliferation was determined by the MIT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) method, immunocytochemical staining, and flow cytometry, and protein expression by Western blot analysis. RSG slowed cell migration distance induced by fetal bovine serum (FBS), decreased cell proliferation initiated by FBS or platelet-derived growth factor-BB (PDGF-BB), and decreased a-smooth muscle actin (alpha-SMA) protein expression induced by transforming growth factor-beta 1 (TGF-beta 1). In addition, RSG incubation reduced the ratio of phospho-extracellular signal-regulated kinases 1/2 (p-ERK1/2) to ERK1/2 expression stimulated by FBS, PDGF-BB, and TGF-beta 1. These findings show that RSG treatment inhibits lung fibroblast migration and proliferation and myofibroblast transdifferentiation stimulated by FBS and growth factors in vitro, which suggests that PPAR gamma agonists could antagonize pulmonary fibrosis and have potential for therapeutic application in pulmonary fibrosis.Respiratory SystemSCI(E)PubMed15ARTICLE2120-1283